If you don't have any parallel, serial or PS/2 devices, and you don't need a floppy, it can't hurt.
That said, most secondary IDE controllers and a lot of newer SCSI controllers require a floppy disk to install Windows on a drive that they control. I.E. - a Highpoint HPT370/372, Promise PDC20278, Silicon Image SIL3112/3114, etc.. You hit F6 during the initial windows install phase, and insert the driver CD - which Windows adds on the fly to its driver database.
So, if you have a legacy-free system, you either need to install the OS on a chipset-level controller, or use a controller that has a native driver (such as the Promise Ultra100, which, when not updated, still suffers from the 127gb limitation). Even some chipset-level SATA controllers, such as the VT6410 integrated into the VT8237 southbridge require drivers, as do Intel's ICH5R in RAID mode.
AFAIK, Windows Server 2003 doesn't have this limitation, but who wants to game on a server OS?
So, what you're stuck is either using your mobo PATA port for a hard drive on which you install windows (so no RAID), or you have to patch the windows install CD itself (which is non-trivial), or you have to have a floppy drive, at which point you have an ISA system, so it's no longer fully legacy-free.
Most system monitoring chips sit on the ISA bus as well.. so I don't think it's possible to get rid of "legacy" level components altogether and, without being able to do so, you still have an ISA bus with all of its performance bottlenecks, if any, present.
All THAT said, I'd love to see someone come out with an i875P / ICH5 or ICH5R system with no ISA bus components whatsoever.. This assumes that the SMBUS components (i.e. system monitoring) are architecturally able to live off the PCI bus, and either have to run ICH5R in ICH5 mode (i.e. just as a SATA controller, not RAID) or you have to use Server 2003, but I'd be willing to make that sacrifice for a cutting-edge system with one less point of failure.